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  ramos
 
  COSBIOS
  FEEDBEADS
 
  General  
 

RAMOS determines the oxygen transfer rate (OTR), the carbon dioxide transfer rate (CTR) and the respiratory quotient (RQ) of microbial, plantal and cell cultures online. The respiration rates (OTR, CTR) are the most suitable measurable variables to quantify the physiological state of fermented cultures (see examples).

The founder of AC Biotec, Tibor Anderlei, is co-inventor of the RAMOS-Technology. Therefore AC Biotec is predestined to offer contract services with the RAMOS-Technology as well as the distribution. Furthermore we provide for our customer a RAMOS-System for rental.

For further questions please contact us: e-mail.


List of advantages :

 
  • substitution of expensive fermentations in stirred bioreactors
  • optimisation of screening conditions in shaken bioreactors
  • non stop applicable (short set-up time)
  • more information about your cultures in shaken bioreactors
  • rapid optimisation of media
  • ensuring a secure scale-up by providing important values (OTR, CTR, RQ, mmax, ...)
  • reduction of the optimisation time and “time to market”
 
MikrOTR measures online the respiration activity in microtiter plates.
  Method  
 

During fermentation a measuring cycle is continually repeated. This measuring cycle is separated into a measuring and a rinsing phase. During the rinsing phase air flows through the measuring flasks. At the beginning of the measuring phase the inlet and outlet valves (V1, V2) of the measuring flasks are closed (Fig. 2). The sustained respiration activities of the microorganisms lead to a change of the partial pressure of oxygen and carbondioxide in the headspace of the particular measuring flasks. At the end of the measuring phase a computer calculates from the changes of the partial pressures the oxygen (OTR) and the carbondioxide transfer rate (CTR) in the particular measuring flasks.

 

 

  

 

The patterns in Fig. 3 show the influence of biological phenomena on the OTR. Fig. 3.1 represents the OTR during unlimited growth of a microbial culture. The OTR rises with the number of cells until the OTR levels off and drops down. This sharp decrease of the OTR indicates the exhaus-tion of the carbon source. This curve in Fig. 3.1 illustrates an ideal course of the OTR. Every deviation from this ideal shape gives the user information about the fermentation conditions of the culture (Fig. 3.2-3.5)). Thus, limitations (3.2, 3.3), inhibitions (3.4) and diauxic growth (3.5) can be easily detected by RAMOS.

  Examples  
 
The list shows an excerpt of biological systems tested with RAMOS:
calculation of profiability :
Cultivation of the yeast Hansenula polymorpha under
 oxygen- and substrate limitation

area normale
procedure		 procedure with
RAMOS		 savings
raw material 2250 mL 290mL 87%
optimisation time 80h 53h 34%
labor time 16.5h 4.1h 75%
list of publications:
  1. Anderlei T., Büchs J., Device for sterile online measurement of the oxygen transfer rate in shaking flasks, Biochem. Eng. J. 7(2), 157-162, 2001
  2. Stöckmann C., Losen M.; Dahlems U., Gellissen G., Büchs J., Definition of reproducible screening conditions case sample Hansenula polymorphia, Chem.-Ing.-Tech. 74(5), 701, 2002
  3. SilberbachM., MaierB., ZimmermannM., BüchsJ., Glucose oxidation by Gluconobacter oxydans: characterization in shaking flasks, scale-up and optimization of the pH profile, Appl. Microbiol. Biotechnol. 62(1), 92-98, 2003
  4. Raval K.N., Hellwig S., Prakash G., Ramos-Plasencia A., Srivastava A., BüchsJ., Necessity of a Two-Stage Process for the Production of Azadirachtin-Related Limonoids in Suspension Cultures of Azadirachta indica, J. Biosc. Bioengng. 96(1), 16-22, 2003
  5. Stöckmann Ch., Losen M., Dahlems U., Knocke Ch., Gellissen G., Büchs J., Effect of oxygen supply on passaging and screening of Hansenula polymorpha strains producing a recombinant protein in test tube cultures, FEMS Yeast Res. 4(2), 195-205, 2003
  6. Stöckmann Ch., Maier U., Anderlei T., Knocke Ch., Gellissen G., Büchs J., The Oxygen Transfer Rate as Key Parameter for the Characterisation of Hansenula polymorpha Screening Cultures, J. Ind. Microbiol. Biotechnol. 30, 613-622, 2003
  7. Maier U., Losen M., Büchs J., Advances in understanding and modeling the gas-liquid mass transfer in shaking flasks, Biochem. Eng. J. 17(3), 155-168, 2004
  8. Danielson P.D., Büchs J., Stöckmann Ch., Fogleman J.C., Maximizing cell densities in miniprep-scale cultures with H15 medium and improved oxygen, Biochem. Eng. J. 17(3), 175-180, 2004
  9. Anderlei T., Zang W., Büchs J., Online respiration activity measurement (OTR, CTR, RQ) in shake flasks, Biochem. Eng. J. 17(3), 187-194, 2004
  10. Lotter St., Büchs J. Utilization of power input measurements for optimisation of culture conditions in shaking flasks, Biochem. Eng. J. 17(3), 195-204, 2004
  11. Peter C.P., Lotter St., Maier U., Büchs J., Impact of out-of-phase conditions on screening results in shaking flask experiments, Biochem. Eng. J. 17(3), 205-216, 2004
  12. Losen M., Lingen B., Pohl M., BüchsJ., Effect of oxygen-limitation and medium composition on Escherichia coli in small-scale cultures, Biotechnol. Progress. (accepted)

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